PaO2, SaO2 and Oxygen Content

How much oxygen is in the blood? The Differences Between
PaO2, SaO2 and Oxygen Content.

In the field of blood gas interpretation, confusion
about PaO2, SaO2 and oxygen content is second only to confusion
about mixed acid-base disturbances.

Arterial PO2 (little 'a')gives us valuable
information about adequacy of gas exchange within the lungs, when (and only when) it is
subtracted from the calculated alveolar PO2 (big A). We use the
Alveolar Gas Equation to calculate PAO2.
The difference between measured PaO2 and calculated PAO2
is called the Alveolar-arterial PO2 difference or 'A-a Gradient' for short.
The A-a gradient answers the important question: Are the lungs
transferring oxygen properly from the atmosphere to the pulmonary circulation? If the A-a
gradient is elevated, the answer is NO. If the A-a gradient is normal is YES. (The A-a
gradient is discussed in detail in Chapter 4).

There is a second, equally important question concerning oxygen and
gas exchange, which is the subject of this section:

How much oxygen is in the blood, and is it adequate for the patient?

The answer here must obviously be based on some oxygen value, but which one?
After all, blood gases give us three different oxygen values:

PaO2

SaO2

Oxygen content (CaO2)

Of these three values, PaO2, or oxygen pressure, is the least
helpful to answer the question about oxygen adequacy in the blood.
The other two values --oxygen saturation and oxygen content --
are more useful for this purpose. I will briefly define
these three terms and then present a more detailed discussion of each, with emphasis
on their inter-relationships.

OXYGEN PRESSURE: PaO2.

Oxygen molecules dissolved in plasma (i.e., not bound to
hemoglobin) are free to impinge on the measuring oxygen electrode. This "impingement" of free
O2 molecules is reflected as the partial pressure of oxygen; if the sample being tested is arterial
blood, then it is the PaO2. Although the number of O2 molecules dissolved in plasma determines,
along with other factors, how many molecules will bind to hemoglobin, once bound the oxygen
molecules no longer exert any pressure (bound oxygen molecules are no longer free to impinge
on the measuring electrode). Since PaO2 reflects only free oxygen molecules dissolved in plasma
and not those bound to hemoglobin, PaO2 cannot tell us "how much" oxygen is in the blood; for
that you need to know how much oxygen is also bound to hemoglobin, information given by the
SaO2 and hemoglobin content.

OXYGEN SATURATION: SaO2.

Binding sites for oxygen are the heme groups, the Fe++-porphyrin
portions of the hemoglobin molecule. There are four heme sites, and hence four oxygen
binding sites, per hemoglobin molecule. Heme sites occupied by oxygen molecules
are said to be "saturated" with oxygen. The percentage of all the available heme binding
sites saturated with oxygen is the hemoglobin oxygen saturation (in arterial blood, the
SaO2). Note that SaO2 alone doesn't reveal how much
oxygen is in the blood; for that we also need to know the hemoglobin content.

OXYGEN CONTENT: CaO2.

Tissues need a requisite amount of O2 molecules for metabolism.
Neither the PaO2 nor the SaO2 provide information on the number of oxygen molecules, i.e., of
how much oxygen is in the blood. (Note that neither PaO2 nor SaO2 have units that denote any
quantity.) Of the three values used for assessing blood oxygen levels, how much is provided only
by the oxygen content, CaO2 (units ml O2/dl). This is because CaO2 is the only value that
incorporates the hemoglobin content. Oxygen content can be measured directly or calculated by
the oxygen content equation (introduced in Chapter 2):

* * *

More on the definitions and distinctions of PaO2, SaO2
and CaO2

You wish it was this simple, huh? I have shown the 3 short paragraphs above to dozens of
students, interns, residents; almost all will say they understand the differences, no
problem. But, when given questions to test their understanding, they flub. So more
instruction is needed (and, yes, a few problems along the way).
Understanding the differences between PaO2, SaO2 and CaO2
is essential to proper blood gas interpretation. By the end
of this and the next chapter -- if you work on all the problems -- you
should be able to teach the subject!

PaO2, the partial pressure of oxygen in the plasma phase of
arterial blood, is registered by an electrode that senses randomly-moving, dissolved oxygen
molecules. The amount of dissolved oxygen in the plasma phase -- and hence the
PaO2 -- is determined by alveolar PO2 and lung architecture only, and
is unrelated to anything about hemoglobin. (With one exception: when there is both anemia
and a sizable right to left shunt of blood through the lungs. In this
situation a sufficient amount of blood with low venous O2 content can
enter the arterial circulation and lead to a reduced PaO2. However,
with a normal amount of shunting, anemia and hemoglobin variables
do not affect PaO2.)

Oxygen molecules that pass through the thin alveolar-capillary
membrane enter the plasma phase as dissolved (free) molecules; most
of these molecules quickly enter the red blood cell and bind with
hemoglobin (Figure 5-1). There is a dynamic equilibrium between the
freely dissolved and the hemoglobin-bound oxygen molecules.
However, the more dissolved molecules there are (i.e., the greater the
PaO2) the more will bind to available hemoglobin; thus SaO2 always
depends, to a large degree, on the concentration of dissolved oxygen
molecules (i.e., on the PaO2).

Figure 5-1. Oxygen pressure, saturation and content. Schematic
shows cross section of lungs and pulmonary circulation. (CO2, nitrogen
and other gas molecules are omitted for clarity.) PaO2 is always slightly
lower than PAO2 because of normal venous admixture, here
represented by a connection between the venous and pulmonary
circulations. See text for discussion. Click on figure to obtain larger image.

Because there is a virtually unlimited supply of oxygen molecules
in the atmosphere, the dissolved O2 molecules that leave the plasma to
bind with hemoglobin are quickly replaced by others; once bound,
oxygen no longer exerts a gas pressure. Thus hemoglobin is like an
efficient sponge that soaks up oxygen so more can enter the blood.
Hemoglobin continues to soak up oxygen molecules until it becomes
saturated with the maximum amount it can hold - an amount that is
largely determined by the PaO2. Of course this whole process is near
instantaneous and dynamic; at any given moment a given O2 molecule
could be bound or dissolved. However, depending on the PaO2 and
other factors, a certain percentage of all O2 molecules will be
dissolved and a certain percentage will be bound (Figure 5-1). In
Figure 5-1, the free or dissolved oxygen molecules register a partial
pressure of 95 mm Hg and the red blood cells contain a total
hemoglobin content of 15 gm/dl.

Each hemoglobin molecule has four Fe++heme sites for binding
oxygen. If there is no interference (as from carbon monoxide, for
example), the free O2 molecules bind to these sites with great avidity.
The total percentage of sites actually bound with O2 is constant for a
given set of conditions, and is the 'saturation of blood with oxygen'.
This is called SvO2 and SaO2 in the venous and arterial circulations,
respectively; in Figure 5-1, the respective values are 75% and 97%.
An SaO2 of 97% simply means that of every 100 hemoglobin binding
sites, 97 are occupied with an oxygen molecule and the other three are
either bound to something else or are unbound.

In summary, PaO2 is determined by alveolar
PO2 and the state of the alveolar-capillary interface, not by the
amount of hemoglobin available to soak them up. PaO2, in turn, determines the
oxygen saturation of hemoglobin (along with other factors that affect the
position of the O2-dissociation curve, discussed below). The SaO2,
plus the concentration of hemoglobin (15 gm/dl in this example),
determine the total amount of oxygen in the blood or CaO2 (see
equation for CaO2). For the variables shown in Figure 5-1, the CaO2
is 20 ml O2/dl.

Clinical Problem 5-1. At 10 a.m. a patient has a PaO2 of 85 mm Hg,
an SaO2 of 98%, and a hemoglobin of 14 gm/dl. At 10:05 a.m.
she suffers a severe hemolytic reaction that suddenly leaves her
with a hemoglobin of only 7 gm/dl. Assuming no lung disease
occurs from the hemolytic reaction, what will be her new PaO2,
SaO2, and CaO2?

(NOTE: Answers to all Clinical Problems are provided at end of this section.)

a) PaO2 unchanged, SaO2 unchanged, CaO2 unchanged

b) PaO2 unchanged, SaO2 unchanged, CaO2 reduced

c) PaO2 reduced, SaO2 unchanged, CaO2 reduced

d) PaO2 reduced, SaO2 reduced, CaO2 reduced

From the forgoing discussion the following observations should
now be apparent.

the less hemoglobin available to bind the dissolved oxygen
molecules, the fewer total number of oxygen molecules will
the blood contain; and

the more hemoglobin available to bind the dissolved oxygen
molecules, the greater total number of oxygen molecules will
the blood contain.

Neither the amount of hemoglobin, nor the binding characteristics
of hemoglobin, should affect the amount of dissolved oxygen, and
hence should not affect the PaO2). Stated another way, the number of
dissolved oxygen molecules is independent of the amount of
hemoglobin or what is bound to it. To repeat one more time (because
it is so important), PaO2 is not a function of hemoglobin content or of
its characteristics, but only of the alveolar PO2 and the lung
architecture (alveolar-capillary interface). This explains why, for
example, patients with severe anemia or carbon monoxide poisoning
or methemoglobinemia can (and often do) have a normal PaO2.

The most common physiologic disturbance of lung architecture,
and hence of a reduced PaO2, is ventilation-perfusion (V-Q)
imbalance. Less common causes are reduced alveolar ventilation,
diffusion block, and anatomic right to left shunting of blood.

Clinical Problem 5.2 State which of the following situations would
be expected to lower PaO2.

a) anemia.

b) carbon monoxide toxicity.

c) an abnormal hemoglobin that holds oxygen with half the
affinity of normal hemoglobin.

d) an abnormal hemoglobin that holds oxygen with twice the
affinity of normal hemoglobin.

e) lung disease with intra-pulmonary shunting.

SaO2 is
determined mainly by PaO2. The relationship between the
two variables is the familiar oxygen dissociation curve (Figure 5-2A).
The dissociation curve is experimentally determined from in vitro
titration of blood with increasing partial pressures of oxygen. At low
oxygen pressures there is relatively little increase in SaO2 for a given
change in PaO2. Above a PaO2 of 20 mm Hg, the rate of change of
SaO2 increases markedly, then slows again beyond a PaO2 of 60 mm
Hg.

PaO2 is the most important (but not the only) determinant of SaO2.
Other determinants of SaO2 for a given PaO2 are conditions that shift
the position of the oxygen dissociation curve left or right, such as
temperature, pH, PaCO2 and level of 2,3-DPG in the blood. Shifts of
the O2-dissociation curve will be discussed further in the next chapter.

For now, consolidate your understanding of the difference between
PaO2 and SaO2. Think of PaO2 as the driving pressure for oxygen
molecules entering the red blood cell and chemically binding to
hemoglobin; the higher the PaO2, the higher the SaO2. Whatever the
SaO2, its value is simply the percentage of total binding sites on
arterial hemoglobin that are bound with oxygen, and can never be
more than 100%.

Figure 5-2 (click to enlarge).

The oxygen dissociation curve, showing PaO2 vs. SaO2
and PaO2 vs. oxygen content for two different hemoglobin values.
P50 is
the PaO2 at which hemoglobin is 50% saturated with oxygen;
normal value is 27 mm Hg. (X represents blood gas values of
a case presented in Chapter 6).

The Arterial oxygen content is shown for two hemoglobin vaues, 15 gm/dl and
10 gm/dl. The relationship between SaO2 and CaO2 for
any given hemoglobin content is linear (excluding the minor influence of dissolved
oxygen with normal PO2 values).

The so-called "steep part" of the O2 dissociation curve is between
20 and 60 mm Hg PaO2. Compared with the flatter portions, small
increases in PaO2 in this region have a much greater effect on
improving SaO2 and therefore O2 content. Figure 5-2A shows the
oxygen dissociation curve for PaO2 plotted against oxygen content for
two hemoglobin concentrations, 15 gm% and 10 gm%. Note that the
shape and position of the curve are the same irrespective of the
hemoglobin content.

SaO2 is unaffected by the hemoglobin content, so anemia does not
lower SaO2. The more hemoglobin, the more oxygen molecules will
be bound in a given volume of blood, but the percentage of available
hemoglobin sites bound to oxygen (the SaO2) depends only on the
PaO2 and curve-shifting factors. Thus, a patient can have a normal
PaO2 and SaO2, but still have a low CaO2 (e.g., with anemia).

CaO2,
unlike either PaO2 or SaO2, directly reflects the total
number of oxygen molecules in arterial blood, both bound and
unbound to hemoglobin. In contrast to the other two variables, CaO2
depends on the hemoglobin content and is directly related to it; other
determinants of CaO2 are the SaO2 (in turn dependent on PaO2 and
position of the oxygen dissociation curve), and the amount of
dissolved oxygen (the PaO2). Since the dissolved oxygen contributes
minimally to CaO2 under physiologic conditions, CaO2 is determined
almost entirely by hemoglobin content and SaO2, and is related
linearly to either variable (Figure 5-2B).

Normal CaO2 ranges from 16 to 22 ml O2/dl. Because PaO2
and/or SaO2 can be normal in certain conditions associated with
hypoxemia, one should always make sure CaO2 is adequate when
assessing oxygenation. About 98% of the normal O2 content is carried
bound to hemoglobin.

The CaO2 component bound to hemoglobin can be calculated by
(Hb x 1.34 x SaO2) and the dissolved component by (.003 x PaO2).
This equation can be used to calculate oxygen content of any blood or
plasma sample.

Figure 5-3 shows two beakers containing liquid open to the
atmosphere. Beaker 1 contains blood with a Hb content of 15
grams%. Beaker 2 contains only plasma (no hemoglobin).
Assuming a barometric pressure of 760 mm Hg (and no water
vapor pressure), calculate the oxygen content in each beaker.

Figure 5-3.

Beaker 1 contains hemoglobin that will combine chemically with
oxygen; hence the oxygen content in beaker 1 consists of bound and
unbound (dissolved) oxygen molecules. In beaker 2 there is no
hemoglobin, just pure plasma; all of its oxygen content must come
from dissolved oxygen.

Dissolved oxygen in both beakers is determined by the PO2 to
which the liquid is exposed and the solubility of oxygen in plasma.
The solubility is .003 ml O2/dl plasma/mm Hg. But what is the PO2?
Because there is no CO2 exchange taking place in either beaker (as
there is in our lungs) and the surface of the liquid is in free contact
with the atmosphere, the PO2in solution is simply
the PO2above the
solution. Given a barometric pressure of 760 mm Hg (dry air), the
PO2 in both beakers is

FIO2 x PB = .21 x 760 mm Hg = 160 mm Hg.

Since the PO2 is equal in both beakers, the O2 content represented
by dissolved oxygen is also the same in both beakers; this content is

?

a) .48 ml O2/dl

b) 2.0 ml O2/dl

c) 4.8 ml O2/dl

To calculate content from dissolved oxygen, substitute the values
for oxygen solubility and PO2:

O2 content of dissolved O2 = .003 ml O2/dl/mm Hg x 160 mm Hg

= .48 ml O2/dl

There is no hemoglobin in beaker 2 so the entirety of its O2
content comes from dissolved oxygen and = .48 ml O2/dl. There is
far more oxygen content in beaker 1 because oxygen molecules
combine chemically with hemoglobin. Once combined, O2 molecules
no longer exert any pressure. As O2 molecules are taken up by
hemoglobin, additional molecules enter the plasma portion of the
blood from the atmosphere. (Remember: Hemoglobin is like a
sponge that soaks up free oxygen molecules and allows many more to
enter the surrounding plasma.) Thus the difference in oxygen content
between the two beakers is the amount of oxygen bound to
hemoglobin.

The oxygen content represented by hemoglobin-bound oxygen in
beaker 1 is

?

a) .48 ml O2/dl

b) 15 ml O2/dl

c) 19.9 ml O2/dl

O2 content is calculated by the oxygen content equation, which in
turn requires knowledge of SaO2, the saturation of hemoglobin with
oxygen. SaO2 is determined by the PO2 to which the blood is exposed
in the lungs (in this case 160 mm Hg) and the position of the oxygen
dissociation curve. With a normally-positioned curve, the SaO2 at this
level of PO2 is approximately 99%. Thus,

Oxygen content (Hb-bound) = Hb x 1.34 x SaO2

= 15 x 1.34 x .99

= 19.9 ml O2/dl

?

What is the total oxygen content of beaker 1? By what factor
is this content greater than that in beaker 2?

The total oxygen content of beaker 1 is of course the sum of the
dissolved and bound fractions, or .48 + 19.9 = 20.38 ml O2/dl. The
total oxygen content of beaker 2 (.48 ml O2/dl) is thus only about
2.4% of that contained in beaker 1. Put another way, beaker 1
contains about 42 times more oxygen than beaker 2.

Clinical Problem 5-4. A healthy man is in the same room as the two
beakers shown in Figure 5-3. If his PaO2 = 100 mm Hg and Hb
content = 15 gms%, what percent of his oxygen content is carried
in dissolved form?

To summarize much of the forgoing discussion:

Although almost all of the oxygen content is chemically bound
to hemoglobin, this quantity is unrevealed by knowing only
the PaO2.

Without knowledge of the hemoglobin content, the PaO2 does
not even give a hint of the total oxygen content.

We need to calculate CaO2 to know the amount of oxygen in
the blood.

Because the body needs a requisite oxygen content for survival,
and PaO2 alone does not indicate oxygen content, a
patient can have normal PaO2 and be starved for oxygen.

Clinical Problem 5-5. For each of the four conditions below, give the
expected changes (increased, decreased, or normal) for PaO2,
SaO2 and CaO2. Assume the subject is breathing ambient air, that
each situation occurred acutely (in less than 24 hours), and that
there is no other abnormal condition.

CONDITION

PaO2

SaO2

CaO2

Severe Anemia

CO Poisoning

Severe V-Q Imbalance

High Altitude

Clinical Problem 5-6. Which patient is more hypoxemic?

Patient A: PaO2 85 mm Hg, SaO2 95%, Hb 7 gm%

Patient B: PaO2 55 mm Hg, SaO2 85%, Hb 15 gm%

Clinical Problem 5-7. Test your understanding by answering the
following statements a-h as either True or False.

a. If the lungs and heart are normal, then PaO2 is affected only
by the alveolar PO2.

b. In a person with normal heart and lungs, anemia should not
lower the PaO2.

c. PaO2 will go up in a patient with hemolysis of red blood cells,
as dissolved oxygen is given off when the cells lyse.

d. As the oxygen dissociation curve shifts to the right, PaO2 rises
since less oxygen is bound to hemoglobin.

e. An anemic patient who receives a blood transfusion should
experience a rise in both SaO2 and CaO2.

f. The PaO2 in a cup of water is zero since there is no blood
perfusing the water.

g. The SaO2 in a cup of water is zero since there is no
hemoglobin present.

h. The CaO2 in a cup of water is zero since there is no
hemoglobin present.